The onset of metabolic syndromes, accompanying diabetes, hypertension, disorders of lipid metabolism, insulin resistance, etc., is rapidly increasing while intra-abdominal fat accumulated obesity increases in modern people due to changes in a living environment. The diseases mutually affect each other, increasing the risk of their occurrence, and are common diseases, which are related with in vivo metabolic changes caused by diverse factors, such as aging, stress and a decline in immune function, etc. Obesity can cause chronic diseases, such as fatty liver, hypertension, diabetes, cardiovascular disease, etc., as well as a physical appearance problem.
At present, 1.7 billion people, equivalent to about 25% of world population, are overweight (BMI>25), and more than 300 million people, including 120 million people in the United States, Europe, and Japan as major markets, are classified as obese (BMI>30) in the West. The United States, where 31% of the entire nation are obese, has the highest rate of obesity among OECD countries, followed by Mexico (24%), the United Kingdom (23%), Greece (22%), Australia (22%), New Zealand (21%), Hungary (19%), Canada (14%), Spain (13%), Ireland (13%), Germany (13%), Portugal (13%), Finland (13%), Turkey (12%), and Belgium (12%). In China, the obese population numbers 70 million, markets relating to body weight control have been rapidly growing, and the total size of the markets is expected to reach about 10 billion yuan. In addition, one in five children in the world are currently affected by childhood obesity, which has emerged as a serious social problem due to a high incidence of the disease. Childhood obesity may be a major cause of diabetes, hypertension, stroke, etc., called ‘lifestyle related diseases’, due to high levels of blood cholesterol and neutral fat, and 80% or more of obese children graduate to adult obesity, leading to serious health problems. Furthermore, puberty may come early for one's age, since excessive fat accumulation stimulates secretion of sex hormones, which may cause growth disorders. Additionally, childhood obesity affects blood circulation and nutrient supply, which may also cause impaired growth.
Non-alcoholic fatty liver disease (NAFLD) refers to a disease, in which neutral fat is accumulated in the liver regardless of drinking, and includes steatosis and non-alcoholic steatohepatitis (NASH). Whereas steatosis is clinically considered a benign disease, NASH as a progressive liver disease, which accompanies inflammation or fibrosis with fatty liver, is considered as a pre-symptomatic disease that causes liver cirrhosis or liver cancer.
Obesity and insulin resistance are representative risk factors for non-alcoholic fatty liver disease. For example, risk factors for hepatic fibrosis progression are obesity (BMI>30), the ratio of liver-function indicators in the blood (AST/ALT>1) and diabetes. Particularly, hepatitis C may proceed into liver cancer in people with hepatitis C who suffer from non-alcoholic fatty liver (NAFL), and thus a need for prevention and treatment of the diseases has emerged as an important issue. 69-100% of non-alcoholic fatty liver patients are obese patients, and 20-40% of obese patients have non-alcoholic fatty liver. Particularly, the prevalence of liver diseases is higher in obese men than in obese women. It has been reported that lesions of non-alcoholic fatty liver appear in 3-30% of adults with normal body weight, as well as obese patients, in Western society. The prevalence of non-alcoholic fatty liver is estimated to be about 20% in Japan, where a dietary life is similar to ours, and 1% of the 20% is estimated to have NASH. Non-alcoholic fatty liver is a problem in obese children as well as adults. 10-77% of obese children (living in Europe, the United States and Asia) show lesions of non-alcoholic fatty liver, which supports the fact that obesity is the most important risk factor for non-alcoholic liver disease.
Anti-obesity drugs, which are sold domestically and abroad, include Xenical (Roche Korea Co., Ltd.), a main component of which is orlistat approved by the U.S. FDA, Reductil (Ilsung Pharm. Co., Ltd.), of which sibutramine is a component, and Exolise (Guju Pharm. Co., Ltd.), which has a catechol ingredient of green tea as a component. Xenical, which inhibits lipase functionality, has side effects on the gastrointestinal system, such as fatty stools, gas generation, reduced absorption of fat-soluble vitamins, etc., and Reductil, which increases the concentrations of serotonin and noradrenalin in the sympathetic nervous system, has side effects, such as headaches, thirst, anorexia, insomnia, constipation, etc. Sales of a considerable number of drugs, which have been developed for anti-obesity, have been prohibited due to serious side effects. For example, aminophylline has been reported to have wide-ranging side effects on the nervous system, circulatory system, and digestive system in spite of its excellent effect of breaking down body fat. Additionally, several drugs, including fenfluramine, dexfenfluramine, topiramate, ephedrine, etc., were not approved as appropriate drugs for obesity treatment, and thus sales thereof was prohibited. Thus, as conventional synthetic drugs have shown limits owing to their side effects, the demand for novel drug compositions for obesity treatment, which are adequate for treatment of chronic diseases by virtue of their safety for long-term use, is increasing.
A number of papers and other patent documents are referenced throughout the present specification, and the citations are marked in the specification. Disclosures of the cited papers and other patent documents are incorporated by references herein in their entirety, whereby level of a technical field pertaining to the present invention and contents of the present invention are clearly explained.